Nutritional supplement based on blackcurrent seed oil

ABSTRACT

The present invention relates to the use of a composition comprising an oil with a high content of essential fatty acids of ω3 and ω6 type, preferably black current seed oil, and at least one compound selected from β-carotene, lycopene, tocopherol and its derivatives, tocotrienols and their derivatives, ascorbic acid and nicotinamide, as a nutritional supplement intended for preventing and/or combating the harmful effects of xenobiotics on the skin, in particular, on the skin&#39;s immune system.

[0001] The present invention relates to the use of a composition comprising an oil with a high content of essential fatty acids of ω3 and ω6 type, preferably black current seed oil, and at least one compound selected from β-carotene, lycopene, tocopherol and its derivatives, tocotrienols and their derivatives, ascorbic acid and nicotinamide as a nutritional supplement intended for preventing and/or combating the harmful effects of xenobiotics on the skin, in particular on the skin's immune system.

[0002] The skin is continually in contact with xenobiotics, which are substances that are referred to as being foreign to the cell's natural metabolic pathways, such as medicinal products, pesticides, pollutants, tobacco or UV. The skin suffers daily attack when it is exposed to these agents, in particular to UV rays which cause immediate damage to the skin, such as sunburn, photosensitivity, or immunosuppression reactions but also long-term effects such as photo-aging or skin tumors.

[0003] Most of these adverse effects are associated with the production of oxygenated free radicals. They have the property of depolymerizing certain skin constituents such as collagen or elastic, or else of degrading membrane lipids or DNAS, which results in the production of endobiotics that are harmful to the skin, such as toxic metabolites or inflammation mediators which finally lead to a loss of integrity of the cell membranes. The action of xenobiotics and endobiotics is particularly important as regards the skin's immune defenses. Specifically, a depletion of the Langerhans cells can result in a penetration of pathogens into the body without the general immune system being alerted. This results, for example, in a higher propensity for the appearance of infections via pathogens.

[0004] The use of compounds capable of inhibiting or neutralizing the action of xenobiotics and endobiotics, in particular, oxygenated free radicals, might make it possible to reduce the skin damage induced.

[0005] Among these compounds, vitamins and essential fatty acids have, in a certain number of in vitro and in vivo studies, shown protective activity with respect to harmful xenobiotics and endobiotics.

[0006] α-Tocopherol has shown that it can prevent the oxidation of polyunsaturated fatty acids, which are essential components of cell membranes and are particularly sensitive to damage induced by free radicals (1). This compound also has anti-inflammatory activity by means of direct action on the enzymatic systems of the arachiodonic cascade (2). Other components belonging to the tocotrienol family (α-, γ-tocotrienols and their derivatives) have shown noteworthy action in preventing cell damage associated with an exposure of the skin and the superficial body growths to free radicals and UV rays (3) and to ozone (4). In addition, it has been demonstrated that the role of tocopherols and tocotrienols is important as regards the activation of the immune system (5).

[0007] Ascorbic acid can also trap the oxygenated free radicals (more particularly singlet oxygen) involved in many oxidative processes which damage cells (6). In addition, α-tocopherol combined with ascorbic acid shows effects on increasing the Minimum Erythemal Dose (7).

[0008] β-Carotene is a vitamin A precursor which acts as a chemical screening agent (with an absorption maximum in the UVA and visible range) and protects against lipid peroxidation (8, 9). It is often used to prevent photodermatoses (10). In general, carotenoids β-carotene, lycopene, leutin, zeaxanthin and astaxanthin) are also resolved in modulating the immune system (WO98/44808). Lycopene is also a free-radical trap (11) and nicotinamide is often used in the same way as a β-carotene against photodermatoses (12).

[0009] Black current seed oil, which contains essential fatty acids of ω3 and ω6 type, has shown a certain level of efficacy in reducing certain inflammatory processes (130.

[0010] In the context of the present invention, it has been found, surprisingly, that a combination between black current seed oil and the above-mentioned compounds has, in a nutritional composition, an advantageous effect for reducing the harmful action of both xenobiotics and endobiotics of the free-radical type or of the type generating free radicals, in particular, reinforcing the skin's immune defenses. After repeated daily administration, such a composition affords protection to the Langerhans cells.

[0011] Descripton

[0012] Thus, the present invention relates to the use of a composition comprising an oil with a high content of essential fatty acids of the type 3 and 6 and at least one compound selected from carotene, lycopene, tocopherol and its derivatives, tocotrienols and their derivatives, ascorbic acid and its derivatives, nicotinamide and a trace element, as a nutritional supplement intended for reinforcing the immune defenses of the skin and the superficial body growths.

[0013] More specifically, this nutritional supplement may be intended for preventing and/or combating the harmful effects of xenobiotics on the skin, in particular, on the skin's immune system, in particular for reducing the cytotoxic effects of xenobiotics on the Langerhans cells. In this sense, the composition according to the inventing is useful for combating or preventing photodermatoses, for improving the skin's tolerance to sunlight and for preventing aging of the skin and the superficial body growths and their disequilibrium due to free radicals.

[0014] In one advantageous embodiment, the composition comprises black current seed oil, since this oil is rich in essential fatty acids of ω3 and ω6 type, in particular α-inoleic acid, α-linolenic acid and γ-linolenic acid. This oil comprises: Palmitic acid C16:0  6-8% Stearic acid C18:0  1-2% Oleic aid ω9 C18:1, 9  9-14% Linoleic acid ω6 C18:2 9, 12 44-51% Linolenic acid ω6 C18:3, 8, 9, 12 15-20% Linolenic acid ω3 C18:3 9, 12, 15 12-14% Stearidonic acid ω3 C18:4, 6, 9, 12, 15  2-4%

[0015] Essentially, the 3 fatty acids have a beneficial effect on erythematic induced by UBV and are useful in the prevention of photocarcinogenesis. The ω6 fatty acids are particularly important in the context of the invention since they participate in keratinization.

[0016] Needless to say, an oil equivalent to black current seed oil in terms of the above-mentioned essential fatty acid composition can be used in the dietary supplement described according to the invention.

[0017] In one preferred aspect of the invention, the composition comprises black current seed oil, β-carotene, lycopene, tocopherol or its derivatives, tocotrienolsor their derivatives, ascorbic acid or its derivatives, andnicotinamide.

[0018] The composition can also comprise a trace element, preferably selenium in any form, in particular, in the form of selenium-containing yeasts.

[0019] Selenium is a co-factor which increases the activity of glutathione peroxidase (GPX), protects cells against the harmful effects of organic and inorganic peroxides, and stabilizes membranes by becoming incorporated into the disulphide bridges, thus leading to a decrease in the amount of arachiodonic acid released during the inflammatory response. Thus, this compound is also useful as a compound for protecting the skin against xenobiotics.

[0020] The composition advantageously comprises at least 25% by weight, preferably about 50% of black current seed oil. It can also comprise:

[0021] at least 5% by weight preferably 15 to 18%, of ascorbic acid;

[0022] at least 4% by weight, preferably about 8%, of lycopene

[0023] at least 2% by weight, preferably about 4%, or carotene;

[0024] at least 1%, preferably about 3%, of nicotinamide;

[0025] and/or at least 1% by weight, preferably about 3%, of nicotinamide;

[0026] A composition according to the invention may thus comprise approximately by weight:

[0027] 53% black current seed oil;

[0028] 4% β-carotene

[0029] 8% lycopene

[0030] 2.2% tocopheryl acetate;

[0031] 15 to 18% ascorbic acid, and

[0032] 3% nicotinamide

[0033] and optionally about 10% by weight of selenium.

[0034] Among the excipients which are added, those preferably selected are yellow beeswax soybean lecithin, glycerol, liquid paraffin and gelatin, preferably of marine nature.

[0035] Needless to say, it is possible to add to the composition any other active compound known in the prior art. Mention may be made, for example, of nucleic acids or nucleotides, amino acids, in particular biologically active sugars, retinoids, plant extracts, in particular from green tea or from soybean, any extracts for plants rich in isoflavones, DHEA and melatonin.

[0036] The composition according to the invention can be in the form of gel capsules, soft capsules, sugar-coated or plain tablets, including delayed forms, suitable for oral administration. Thus, the invention relates to a composition as defined above.

KEY TO THE FIGURES

[0037]FIG. 1 shows efficacy of the oral supplement according to the invention on an erythematic induced by UV. The measurement of the variation in the 1-month and 3-month minimum erythemal dose is indicted.

[0038]FIG. 2 depicts efficacy of the oral supplement according to the invention on an erythematic induced by UV. The measurement shown is of the variation in the average intensity of erythema at 3 months (oral composition+factor 16 antisun cream and placebo+factor 16 antisun cream).

[0039]FIG. 3 depicts the efficacy of the oral supplement according to the invention the depletion of Langerhans cells induced by UV. The measurement is of the variation in the number of Langerhans cells (p<0.05).

[0040]FIG. 4 shows the effficacy of the oral supplement according to the invention on lipid peroxidation. The measurement is of the variation in the amount of squalling peroxides.

EXAMPLE 1 Preferred Composition No. 1 of the Invention

[0041] ADD

[0042] Measurements

[0043] The Minimum Erythermal Dose (MED), or weakest perceptible redness with clearly defined edges, was determined on the back of the volunteers participating in the study, according to the recommendations of Colipa, before, 1 month after, and 3 months after the start of the oral supsplementatiaon.

[0044] The capacity imparted by this supplementation to reinforce the protection afforded by an antisun cram (sun protection factor 16) was furthermore evaluated before and after the 3 months of treatment and was compared with the efficacy of the anti-sun cream alone.

[0045] Biopsies

[0046] Superficial skin samples were taken from the lower back of 10 volunteers from each group, using a circular bistoury (punch) 4 mm in diameter, 24 hours after irradiation with 1 MED.

[0047] The biopsies were then fixed with Bouin's fluid, included in paraffin and then sliced in series in order to be developed by immunohistochemistry to reveal the Langerhans cells (use of mouse clone 010 IgG1 monocolonal antibody, from the Immunotechlaboratory, which recognizes a specific membrane marker of the Langerhans cell, CD1a).

[0048] Results

[0049] All the results and the statistical comparisons are given in FIGS. 1-4 herein below.

[0050] The oral supplementation studied significantly reinforces the skin's resistance to sunlight, compared with its placebo:

[0051] increase in the minimum erythemal dose (FIG. 1),

[0052] increase in the efficacy of a topical antisun screening agent (FIG. 2)

[0053] effect on the skin's immune system, by reducing the depletion of the Langerhans cells which is induced by UV (FIG. 3),

[0054] scavenging of the free radicals induced by UV (squalene hydroxyperoxides) (FIG. 4).

[0055] This combination of vitamins (α-tocopherol, ascorbic acid, β-carotene, lycopene and nicotinamide) and of black current seed oil, which contains essential fatty acids, thus appears to be indicated in the prevention of adverse effects induced by xenobiotics, in particular, for reinforcing the skin's immune defenses. 

What is claimed is:
 1. A composition for reinforcing the immune defenses of the skin and superficial body growths comprising: (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotene, lycopene, tocopherol, tocopherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trace elements and mixtures thereof.
 2. A composition according to claim 1 wherein said composition further comprises black current seed oil.
 3. A composition according to claim 2 wherein said composition comprises black current seed oil, β-carotene, lycopene, tocopherol or tocopherol derivatives, ascorbic acid and nicotinamide.
 4. A composition according to claim 1 wherein one of said trace elements is selenium.
 5. A composition according to claim 2 wherein said composition comprises at least about 25% by weight of black current seed oil.
 6. A composition according to claim 5 wherein said composition comprises at least about 50% by weight of black current seed oil.
 7. A composition according to claim 1 wherein said composition comprises at least about 5% by weight of ascorbic acid.
 8. A composition according to claim 7 wherein said composition comprises between about 15 and 18% by weight of ascorbic acid.
 9. A composition according to claim 1 wherein said composition comprises at least about 4% by weight of limonene.
 10. A composition according to claim 1 wherein said composition comprises at least about 8% by weight of lycopene.
 11. A composition according to claim 4 wherein said composition comprises at least about 5% by weight of selenium.
 12. A composition according to claim 11 wherein said composition comprises at least about 10% by weight of selenium.
 13. A composition according to claim 1 wherein said composition comprises at least about 2% by weight of β-crotene.
 14. A composition according to claim 13 wherein said composition comprises at least about 4% by weight of β-carotene.
 15. A composition according to claim 13 herein said composition comprises at least about 1% by weight of nicotinamide.
 16. A composition according to claim 15 wherein said composition comprises at least about 3% by weight of nicotinamide.
 17. A composition according to claim 1 wherein said composition comprises at least about 1% by weight of tocopherol or tocopherol derivatives.
 18. A composition according to claim 1 wherein said composition comprises at least about 2% by weight of copherol derivatives.
 19. A composition according to claim 1 wherein said tocopherol derivative is tocopheryl acetate.
 20. A composition according to claim 1 wherein said composition comprises about 53% of black current seed oil, about 4% β-corotne, about 8% lycopene, about 2.2% tocopheryl acetate, from about 15 to about 18% sscorbic acid and about 3% nicotinamide.
 21. A composition according to claim 1 wherein said composition comprises black current seed oil, carotene, lycopene, tocoheryl acetate ascorbic acid and nicotinamide.
 22. A composition according to claim 20 wherein said composition further comprises about 10% selenium.
 23. A composition according to claim 1 wherein said composition further comprises an excipient selected from the group consisting of yellow beeswax, soybean lecithin, glycerol, liquid paraffin and gelatin and mixtures thereof.
 24. A composition according to claim 1 wherein said composition is in the form of gel capsules suitable for oral administration.
 25. A method of reinforcing the immune defenses of the skin and superficial body growths comprising administering orally to a mammal a composition comprising; (a) (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotne, lycopene, tocoherol, tocopherol derivative, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trace elements and mixtures thereof.
 26. a method of reducing the cytotoxic effects of xenobiotics or Langerhans cells comprising administering orally to a mammal comprising: (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotene, lycopene, tocoherol, tocopherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, asocribc acid derivatives, nicotinamide, one or more trace elements and mixtures thereof.
 27. a method of combating or preventing photdermatoses comprising administering orally to a mammal a composition comprising; (a) (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotnee, lycopene, tocopherol, tocopherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trace elements and mixtures thereof.
 28. A method of improving the skin's tolerance to sunlight comprising administering orally to a mammal a composition comprising; (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of carotene, lycopee, tocopherol, cooherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trade elements and mixtures thereof.
 29. a method of preventing or treating aging of the skin comprising administering orally to a mammal an essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotne, lycopene, tocoherol, tocopherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trace elements and mixtures thereof.
 30. A method of preventing or treating superficial growths of the skin comprising administering orally to a mammal a composition comprising: (a) an oil comprising a high content of essential fatty acids of the type ω3 and ω6; and (b) at least one compound selected from the group consisting of β-carotene, lycopene, tocopherol, tocopherol derivatives, tocotrienol, tocotrienol derivatives, ascorbic acid, ascorbic acid derivatives, nicotinamide, one or more trace elements and mixtures thereof. 